Androgen signaling via sympathetic neurons regulates allergic pulmonary inflammation.

Sex differences in the rates of asthma onset and remission suggest that sex hormones may play an important role in the pathogenic mechanism underlying certain forms of asthma. Here, we demonstrate that increased endogenous androgen production in male mice can mitigate pulmonary type 2 inflammation after repeated allergen exposures during early life. Building on previous work showing that immune cells can respond to androgen signaling, we report that androgens also promote pulmonary sympathetic innervations, which can dampen type 2 inflammation via the neurotransmitter norepinephrine. Ablation of the androgen signal in sympathetic neurons is sufficient to disturb the establishment of sympathetic structures in the lungs of male mice, thereby amplifying type 2 inflammatory responses to allergens. Thus, an endocrine-neuroimmune axis contributes to the sexual dimorphism of allergic asthma during development.